Effects of acute caloric restriction on skeletal muscle homeostasis in ageing mice

New Perspectives on the Physiological Basis of Muscle Loss (University of Exeter, UK) (2024) Proc Physiol Soc 60, C06

Oral Communications: Effects of acute caloric restriction on skeletal muscle homeostasis in ageing mice

Harrison Gallagher1, Peter Tickle1, Paul Hendrickse1, Emily Storey1, Marcelo Gomes Pereira1, Nadira Yusupovna Yuldasheva1, Lee Roberts1, Thomas Scott Bowen1,

1School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds Leeds United Kingdom, 2School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester Manchester United Kingdom, 3Faculty of Health and Medicine, University of Lancaster Lancaster United Kingdom, 4Faculty of Medicine, University of Leeds Leeds United Kingdom,

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Background: Ageing is associated with a progressive decline in skeletal muscle mass and strength termed sarcopenia, which can influence both limb and respiratory muscles. However, established pharmacological interventions to treat sarcopenia remain limited. Lifelong caloric restriction (CR) of moderate deficits (~40%) can reduce sarcopenia in ageing rodents, but in humans extended CR periods are limited by both desire and commitment.  

 

Objectives: To characterise the effects of an acute and mild caloric restriction intervention on limb and respiratory muscle properties in ageing mice.

 

Methods: Older male C57BL/6 mice (23 months; n=9) were subject to 4 weeks of caloric restriction (10-25% reduction in food intake) and were compared to ad libitum chow-fed control mice including age-matched (n=7) or young (10 months; n=7). Following euthanasia, a limb muscle (EDL) was evaluated for wet-mass and fibre cross-sectional area (via immunohistochemistry), whereas diaphragm bundles were isolated and directly stimulated in vitro across the force-frequency relationship to examine contractile function.

 

Results: Ageing was associated with an 18% reduction in EDL mass vs young controls (P=0.08), with calorie-restriction further decreasing wet-mass by 24% (P<0.01) and myofiber size by 14% (P=0.079) vs control younger mice. However, twitch specific force increased by 32% (P<0.01) following caloric restriction in aged mice (5.5 vs. 7.2 N/cm2).

 

Conclusion: Acute caloric restriction in ageing mice was associated with atrophy in the limb muscle but improved contractile function in respiratory muscle. Mild and acute caloric restriction during ageing may have divergent structural and functional effects between limb and respiratory muscles.



Where applicable, experiments conform with Society ethical requirements.

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